Distinct Effects of Sevoflurane and Propofol on Vascular Permeability In Vitro and in a Mouse Model.

Summary

At clinically relevant doses, sevoflurane—but not propofol—increased endothelial permeability in vitro and pulmonary vascular leakage in mice. Mechanistically, sevoflurane activated HIF-1α, upregulated VEGF, and HIF-1α knockdown abolished permeability changes, identifying a drug-specific HIF-1α/VEGF pathway.

Key Findings

• Sevoflurane disrupted endothelial monolayers and increased transwell permeability in HUVECs and mouse pulmonary endothelial cells.
• In mice, sevoflurane increased AngioSense dye accumulation in lung by 1.8-fold versus control, indicating pulmonary vascular leakage; propofol did not.
• Sevoflurane activated HIF-1α and upregulated VEGF in vitro and in vivo; HIF-1α knockdown abolished permeability and VEGF changes.

Clinical Implications

Consider propofol-based TIVA in patients at high risk of pulmonary edema/vascular leak (e.g., ARDS risk, severe sepsis) and exercise vigilance when using sevoflurane in such populations; monitor oxygenation and lung water closely.

Limitations

• Preclinical models; no direct clinical outcome data
• Focus on pulmonary vascular bed; generalizability to other organs or human perioperative settings requires validation

Future Directions

Translational studies comparing volatile vs TIVA strategies in high-risk surgical patients with endpoints of vascular leak and pulmonary complications; exploration of HIF-1α modulation as a protective strategy.